Immunometabolic Mechanisms of Blood Flow Restriction (BFR) Training After Anterior Cruciate Ligament Reconstruction

Anterior Cruciate Ligament Reconstruction Clinical Trial

Official title:

Immunometabolic Mechanisms of Blood Flow Restriction Training After Anterior Cruciate Ligament Reconstruction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05012982
• Other study ID #: 2000030152
• Status: Recruiting
• Phase: N/A
• Start date: February 16, 2023
• Est. completion date: January 1, 2025

Study information

• Verified date: February 2024
• Source: Yale University
• Contact: Rachel Perry, PhD
• Phone: 203-506-5179
• Email: rachel.perry[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a crossover phase 4 study to evaluate the impact of blood flow restriction on immunometabolism and gene expression in immune cells in individuals undergoing rehabilitation from anterior cruciate ligament reconstruction.

Description:

This is a single-blind crossover phase 4 study in which participants will be randomized as to the order in which each of two sessions are completed. Although all analyses will be performed by a blinded investigator and participants will wear an uninflated AirBand as the control intervention during the session in which BFR is not performed, participants will likely know which of the two interventions is being performed on which study day. The AirBands will be placed at each of the two training sessions and inflated while an ultrasound probe is placed over the femoral artery. The cuff will be inflated until the artery reaches 60% occlusion. The force will be applied using a wireless Bluetooth signal; participants will not be asked to adjust the device. Participants will be observed by a certified Personal Therapist throughout the training session in order to determine compliance and ensure safety as is standard protocol for a physical therapy session. The study team hypothesizes that the BFR will: - Promote an anabolic immunometabolic signature, reflected in the composition of serum amino acid concentrations and anabolic hormone content - Enhance anaerobic glycolysis in leukocytes (which has been associated with increased activation in other settings (Marelli-Berg and Jangani, 2018; Pearce and Pearce, 2013)) - Increase leukocyte glucose and pyruvate concentrations, which corresponds to acute energy provision to promote repair

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 1, 2025
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for two study visits at least 1 week apart

3. All genders, between 18 and 60 years of age

4. In good general health without any underlying medical conditions or prior injury that would place the subject at risk of further injury/illness by participating in the study

Exclusion Criteria:

1. Serious medical conditions including cardiovascular, metabolic (diabetes), rheumatologic, pulmonary, or musculoskeletal.

2. Multiple ligament ruptures or trauma

3. Rheumatoid arthritis or other significant comorbidities

4. Lower extremity vascular pathology, including history of deep vein thrombosis

5. Those with a history of sickle cell trait or disease

6. Use of anticoagulant medications

7. Pregnancy

8. Treatment with another investigational drug or other intervention within one month of Study Day 1

9. Current smoker or tobacco use within 3 months of Study Day 1

10. Febrile illness within 2 weeks of Study Day 1

Related Conditions & MeSH terms

• Anterior Cruciate Ligament Reconstruction

Intervention

Device:
• AirBand
The AirBands will be placed at each of the two training sessions and inflated while an ultrasound probe is placed over the femoral artery. The cuff will be inflated until the artery reaches 60% occlusion. The force will be applied using a wireless Bluetooth signal; participants will not be asked to adjust the device. Participants will be observed by a certified Personal Therapist throughout the training session in order to determine compliance and ensure safety as is standard protocol for a physical therapy session.
• uninflated AirBand
Uninflated AirBand will be used as the control intervention during the session in which BFR is not performed

Locations

Country	Name	City	State
United States	Yale New Haven Hospital	Milford	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Leukocyte metabolic gene expression	Gene expression measured by RNAseq. Because of the nature of RNAseq it is not possible to provide a comprehensive list of gene expression that will be measured; however, genes of particular interest include Slc2a3, Slc2a1, Slc2a4, Slc16a3, PC, Pdha1, Acc1, Fasn.	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Primary	Change in leukocyte substrate preference	Fractional contributions of glucose and fatty acids to total mitochondrial oxidation will be measured. Each can fuel between 0 and 100% of total mitochondrial oxidation.	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Primary	Change in amino acids concentrations	Concentrations of all amino acids (alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamate, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine). Amino acid concentrations may be between 1 and 500 uM. Higher amino acid concentrations may indicate greater muscle breakdown (proteolysis).	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Primary	Change in glucose concentrations	Glucose may be between 4 and 15 mM. Higher glucose may be indicative of diabetes.	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Primary	Change in lactate concentrations	Lactate may be between 0.2 and 8 mM. Higher lactate may be indicative of a more intense exercise response.	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Primary	Change in fatty acid concentrations	Saturated and unsaturated fatty acid concentrations will be measured. Each fatty acid may range from 0 to 5 mM. Increased fatty acid concentrations may be indicative of a greater stress response to exercise.	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Primary	Change in insulin concentrations	Insulin may range from 0 to 100 uU/ml. Higher insulin may indicate a greater stress response.	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Primary	Change in glucagon concentrations	Glucagon may range from 0 to 500 pM. Higher glucagon may indicate lower blood glucose concentrations.	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Primary	Change in catecholamines concentrations	Epinephrine and norepinephrine (also known as adrenaline and noradrenaline) will be measured. They can range from 0-1000 nM. Higher catecholamide concentrations may indicate a greater stress response to training.	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Secondary	Whether a baseline immunometabolic blueprint predicts the immunometabolic response to resistance training or to BFR.	Correlation between Outcomes 1-9 at 0, 30 and 60 minutes after training, to Outcomes 1-9 before training	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Secondary	Whether the immunometabolic response correlates with patient-reported soreness following a physical therapy training session.	the soreness scale is 0 to 10, with 0 as no pain or soreness and 10 as pain or soreness as bad as it could possibly be.	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise
Secondary	Change in creatine kinase	Creatine kinase concentration	Baseline, 0 (immediately at the end of the exercise session), 30, and 60 minutes post exercise